Recent theories of the etiology of drug addiction suggest that craving and relapse are linked to a Pavlovian process whereby the drug user learns to associate environmental cues with drug effects. If the individual returns to an environment where the drug is expected, but not administered, he may experience an adverse conditioned physiological reaction similar to withdrawal which prompts renewed drug taking. Pavlovian conditioned responses have also been shown to contribute to the growth of drug tolerance. No study, however, has yet shown a direct link between conditioned drug responses and self-administration. Using an animal (rat) model for intravenous self-administration of morphine, we propose several studies to examine the interplay between Pavlovian conditioning and operant self-administration. Using both dependent and nondependent rats, several studies will assess the role of critical conditioning parameters (interstimulus interval, drug dose, number of trials) on the classical conditioning of heart rate and body temperature by morphine and naloxone. We will also see whether the environment associated with drug self-administration becomes capable of eliciting conditioned physiological responses and whether such responses are correlated with the frequency of self-administration. Finally, we will manipulate the Pavlovian value of contextual cues by pairing them with morphine or naloxone; the behavioral impact of this conditioning on self-administration will then be assessed. The results of these studies will permit us to evaluate suggestions that Pavlovian conditioned responses play a critical role in the development, maintenance, elimination and relapse of drug addiction. The long term objective of this research is to increase our understanding of the biobehavioral processes that contribute to the etiology of drug abuse and dependence. This understanding should help us to recognize increased risk of drug abuse, to devise more efficient and effective treatments for drug addiction and to outline more effective prevention strategies.